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Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

2016; Cell Press; Volume: 30; Issue: 1 Linguagem: Inglês

10.1016/j.ccell.2016.05.004

1878-3686

Jakob Hedegaard, Philippe Lamy, Iver Nordentoft, Ferrán Algaba, S. Høyer, Benedicte Parm Ulhøi, Søren Vang, Thomas Reinert, Gregers G. Hermann, Karin Mogensen, Mathilde Borg Houlberg Thomsen, Morten Muhlig Nielsen, Mirari Márquez, Ulrika Segersten, Mattias Aine, Mattias Höglund, Karin Birkenkamp‐Demtröder, Niels Fristrup, Michael Borre, Arndt Hartmann, Robert Stöhr, Sven Wach, Bastian Keck, Anna Katharina Seitz, Roman Nawroth, Tobias Maurer, C. Tulić, Tatjana Simić, Kerstin Junker, Marcus Horstmann, Niels Harving, Astrid Petersen, M. Luz Calle, Ewout W. Steyerberg, Willemien Beukers, Kim E.M. van Kessel, Jørgen Bjerggaard Jensen, Jakob Skou Pedersen, Per‐Uno Malmström, Núria Malats, Francisco X. Real, Ellen C. Zwarthoff, Torben F. Ørntoft, Lars Dyrskjøt,

Cancer Genomics and Diagnostics

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.